Down syndrome is a model for the study of Alzheimer's disease because almost 100% of middle-aged individuals with this condition show a specific pathogenic process that follows a predictable course of development. This study will develop and refine a paradigm for measuring signs of Alzheimer's disease in Down syndrome. The method proposed and developed here measures brain pathology and functional decline due to Alzheimer's disease. This research method combines a relatively new form of positron emission tomography, called [F-18]FDDNP PET (2-(1-{6- [(2-18F-fluoroethyl) (methyl) amino] -2-napthyl] ethylydene malononitrile, with (1) comparative neuropsychological test methods derived from animal studies of aging and cognition and (2) functional brain imaging (PET-FDG). The [F-18]FDDNP PET involves a radiolabeled probe that binds to A[unreadable] plaques and neurofibrillary tangles and will be used to measure, in vivo, brain pathology in Down syndrome. Comparative neuropsychological tests with proven validity for people suffering from severe levels of cognitive impairment (e.g., mental retardation) will also be used. Rate of glucose metabolism based on PET-FDG has been effective in distinguishing individuals by stage of Alzheimer's disease, including individuals with Down syndrome. A cross-sectional design will include 40 adults with Down syndrome (20 demented and 20 unaffected), 20 individuals from the general community diagnosed with probable Alzheimer's disease, and 20 healthy controls. Results will extend preliminary studies and are expected to provide the means to more effectively track disease progress and assess treatment outcome. Consequently, this new method of detection stands not only to improve diagnosis and treatment for people with Down syndrome, but for the general population as well. PUBLIC HEALTH RELEVANCE: Many people with Down syndrome suffer from Alzheimer's disease because of their genetic make-up. Early detection is important to help slow disease progression. This study is a first-ever attempt to assess the two major signs of Alzheimer's disease in the brains of living adults with Down syndrome. Results of this study stand to improve early detection of Alzheimer's disease in Down syndrome and in other individuals.